| 1. |
- Mullins, Niamh, et al.
(författare)
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GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
- 2019
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
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Tidskriftsartikel (refereegranskat)abstract
- Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
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| 2. |
- Walfridsson, Håkan, et al.
(författare)
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Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial
- 2015
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Ingår i: Europace. - : Oxford University Press (OUP): Policy B - Oxford Open Option B - CC-BY. - 1099-5129 .- 1532-2092. ; 17:2, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Aims The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. Methods and results During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. Conclusion Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale.
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| 3. |
- Hjorth Larsen, Ask, et al.
(författare)
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The atomic simulation environment-a Python library for working with atoms
- 2017
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Ingår i: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 29:27
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Forskningsöversikt (refereegranskat)abstract
- The atomic simulation environment (ASE) is a software package written in the Python programming language with the aim of setting up, steering, and analyzing atomistic simulations. In ASE, tasks are fully scripted in Python. The powerful syntax of Python combined with the NumPy array library make it possible to perform very complex simulation tasks. For example, a sequence of calculations may be performed with the use of a simple 'for-loop' construction. Calculations of energy, forces, stresses and other quantities are performed through interfaces to many external electronic structure codes or force fields using a uniform interface. On top of this calculator interface, ASE provides modules for performing many standard simulation tasks such as structure optimization, molecular dynamics, handling of constraints and performing nudged elastic band calculations.
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| 4. |
- Liu, Xueping, et al.
(författare)
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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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| 5. |
- Martin, Joanna, et al.
(författare)
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A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:12, s. 1044-1053
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.METHODS: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls).RESULTS: Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r(g) estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15).CONCLUSIONS: Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.
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